Sudden cardiac death remains one of our nation's major health problems. When rapid ventricular tachyarrhythmias or fibrillation are terminated immediately by appropriate pharmacological or electrical techniques, the patient often has an excellent chance for long-term survival. An understanding of the electrophysiological mechanisms involved in the development of potential lethal cardiac arrhythmias that frequently accompany myocardial ischemia are necessary to devise therapeutic regimes for the treatment and prevention of electrical cardiac deaths. The cardiac electrophysiological investigations in this application will employ animal models of acute and chronic myocardial ischemia as investigations of patients having ventricular tachyarrhythmias and/or primary ventricular fibrillation. By this multidisciplinary approach, new findings will be obtained concerning the electrophysiological mechanism(s) involved in the development and termination of potentially lethal cardiac arrhythmias. Also, electrophysiological factors identifying patients who are at high risk of developing primary ventriculr fibrillation will be investigated by comparing and contrasting findings in patients with ventricular tachyarrhythmias only some of whom have had documented episodes of primary ventricular fibrillation. The proposed animal studies will employ a system for recording simultaneously 24 cardiac electrograms from sites within the central and peripheral portions of the ischemic areas as well as from normal myocardial tissue during both occlusion and release of various coronary vessels in the canine ischemic model. Those electrophysiological phenomena leading up to the development of ventricular fibrillation upon occlusion and/or release will be determined. A more thorough understanding of the cardiac electrophysiological mechanisms leading to lethal cardiac arrhythmias cannot help but lead towards the development of more effective preventive therapy of primary ventricular fibrillation and lethal cardiac arrhythmias.